Effects of non-opioid antitussives on epileptiform activity and NMDA responses in hippocampal and olfactory cortex slices.
Three commonly used antitussive compounds were tested for their ability to block epileptiform activity recorded extracellularly from hippocampal and olfactory cortex slices maintained in vitro. Antitussives were bath-applied to brain slices either before or after epileptiform activity was induced. Dextromethorphan (DM) prevented electrically evoked epileptiform afterdischarges and arrested spontaneous bursting induced by exposure to added NMDA or to Mg2(+)-free medium. In contrast, caramiphen (CM) and carbetapentane (CB) were effective against epileptiform activity induced by Mg2(+)-free medium, but not by NMDA. Atropine was not effective in blocking epileptiform activity at concentrations 10 times the effective concentration of CM, which has known cholinolytic activity. Our results suggest that all these antitussives exert their anticonvulsant action at the DM binding site. Neither cholinolytic activity nor antagonism of the NMDA receptor-channel complex appears to be necessary for antitussives to prevent or arrest epileptiform activity. DM appears to have a separate NMDA-antagonist property in addition to its actions at the DM site. Our neurophysiological evidence supports the hypothesis that these antitussives have anticonvulsant properties independent of any action at the NMDA receptor-channel complex.
Apland
J P
JP
Neurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Braitman
D J
DJ
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D003517:Cyclopentanes / Q000494:pharmacology; D003915:Dextromethorphan / Q000494:pharmacology; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
D000996:Antitussive Agents; D003517:Cyclopentanes; C018861:carbetapentane; D016202:N-Methylaspartate; D003915:Dextromethorphan; C004519:caramiphen; D008274:Magnesium